Quad Therapy for Chronic Kidney Disease is on the Horizon

When I was a budding young pharmacist in training, the options for attenuating the progression of chronic kidney disease (CKD) were limited to the renin-angiotensin-aldosterone system (RAAS) inhibitors. RAAS inhibitors include angiotensin-converting-enzyme (ACE) inhibitors and angiotensin 2 receptor blocks (ARBs).That has all changed within the last few years with the explosion of data from newer drug classes. The SGLT2 inhibitors were first, and these agents are now FDA-approved to attenuate eGFR decline and reduce the rate of adverse cardiovascular events in patients with CKD. Next came finerenone, which now carries a similar FDA indication for renal protection and CVD reduction in patients with CKD. Finally, recent data has linked GLP-1 agonists to favorable outcomes in patients with CKD.

As regular readers of this column are well aware, the era of quad therapy for heart failure has already arrived. However, the idea of stacking therapies for additional risk reduction in CKD has not been widely discussed or explored in clinical evidence before. In this week’s installment of Talking Therapeutics, we cover a paper that addresses this key evidence gap.

Talking Point: Big Win for Quad Therapy

In a new study, data was combined from several randomized clinical trials and evaluated using actuarial methods to estimate the absolute risk reductions with a combination of SGLT2i, GLP-1 RA, and finerenone in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g).

The study found the combination of SGLT2i, GLP-1 RA, and finerenone was associated with a hazard ratio of 0.65 (95% CI, 0.55–0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) when compared to monotherapy with a RAAS inhibitor. This corresponded to an estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0–5.7), with a number needed to treat of 23 (95% CI, 18–33). There were also projected gains in freedom from chronic kidney disease progression by 5.5 years [95% CI, 4.0–6.7]).

Talking Point: Still Just the Dawn of an Era

This regimen of quad therapy has yet to be ready for prime time, as this data was just a statistical model of what could happen if these drugs were combined. Also, 3 of these medications carry a branded copay, so the costs to the patient and society must be delineated through pharmacoeconomic studies before this regimen can be pursued.

These limitations notwithstanding, this paper offers a glimpse into a potentially promising future for patients with diabetes and CKD (as defined by the presence of albuminuria).